A gene signature in histologically normal surgical margins is predictive of oral carcinoma recurrence
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE31056 | GEO | 2011/08/03
SECONDARY ACCESSION(S): PRJNA144853
REPOSITORIES: GEO
Similar Datasets
Project description:Samples were prospectively collected from patients with histologically normal surgical resection margins. 96 tissue samples (histologically normal margins, oral carcinoma and adjacent normal tissues) from 24 patients comprised the training set. Our study design was guided by the hypothesis that the expression of genes present in oral squamous cell carcinoma (OSCC) but not in healthy oral tissues would be indicative of recurrence in advance of histological alteration. We used meta-analysis of five published microarray data sets (GEO accession GDS2520, Kuriakose et al. 2004; GDS1584, Toruner et al. 2004; GSE6791, Pyeon et al. 2007; GSE9844, Ye et al. 2008; and GSE10121, Sticht et al. 2008), in conjunction with the current training set, to identify genes reliably over-expressed in OSCC. This reduced gene set was used to train a risk model to predict recurrence based on over-expression of a subset of these genes in histologically normal surgical resection margins. Validation of the risk signature was performed using quantitative real-time reverse-transcription PCR in an independent set of 136 samples from an independent cohort of 30 patients. This was a case-only design involving a training set of 23 tumors and 73 margins from 24 patients with squamous cell carcinoma of the tongue.
2011-08-02 | E-GEOD-31056 | biostudies-arrayexpress
Project description:Comparison of polysomal profiles of murine adult olig2 cortical progenitors, murine tumor olig2 cells derived from hPDGF-B-driven glioblastomas, and murine olig2 proliferative recruited glioma cells contributing to the tumor mass but not derived from the cell of origin An unbiased way to define a cell population lies in identification of its gene expression signature and subsequent comparison to gene expression signatures of known normal or cancer cells to define its position on the axis of tumorigenesis. To quantify similarities and differences in the expression profiles of recruited cells and tumor cells using microarray analysis, we used the bacTRAP technology that allows immunoprecipitation of polysomes from specific cell types in vivo (Heiman et al 2008, Doyle et al 2008). We compared polysomal expression profiles of hPDGFb-driven Ntv-a Ink4a/Arf+/- olig2 mouse glioma cells representing a histologically defined glioma population, recruited olig2 cells derived from Ink4a/Arf+/- olig2 RP-eGFP mice transplanted with non-fluorescent glioma cells, and normal adult cortical olig2 mouse progenitors, using Affymetrix 430 mouse 2.0 chips and Genespring GX10 software (Doyle et al 2008, Heiman et al 2008). Translational profiles of recruited olig2 cells and glioma olig2 cells were similar to each other and clearly distinct from the normal olig2 progenitors, majority of the differences accounted for by the “statistically significantly changed” set of mRNAs (ANOVA, p<0.05), and sample clustering reduced upon removal of the ANOVA-tested mRNA set. Unsupervised hierarchical mRNA clustering likewise indicated that recruited olig2 cells clustered more closely to glioma olig2 cells. The caveat is that olig2 expression in the adult normal brain of bacTRAP olig2 RP-eGFP mice labels both progenitors and mature oligodendrocytes, while recruited and tumor olig2 cells are almost entirely progenitors; therefore, some of the differences seen in the comparative analysis of normal, tumor and recruited olig2 cells may in part result from the shift in relative abundance of different progenitor and mature olig2 cell populations. Normal olig2 progenitors were collected from three replicates of pooled cortices of three olig2 RP-eGFP bacTRAP reporter mice. Mouse gliomas induced by injection of a non-fluorescent RCAS-hPDGFb (Shih et al 2004) or by transplantation of muring glioma cells derived from Ntv-a gliomas induced by the non-fluorescent RCAS-hPDGFb were collected from Ntv-a olig2 RP-eGFP bacTRAP reporter mice and immunoprecipitated; each tumor was processed as a separate sample. Briefly, mouse tissues were collected into ice-cold cyclohexamide-containing buffer, homogenized, cells were lysed in NP-40 and DHPC-containing buffer, centrifuged at 20,000g for 15 min, supernatant incubated with anti-eGFP-conjugated protein G beads 30 min at 4C, washed and RNA collected using Trizol reagent as per manufacturer’s instructions (Doyle et al., 2008; Heiman et al., 2008). RNA was purified, concentrated using Qiagen RNeasy kit, its quality confirmed by Agilent Bioanalyzer, 15ng per sample amplified using Affymetrix Two-Cycle Amplification kit and hybridized to Affymetrix 430 mouse 2.0 chips as described in Doyle et al., 2008; Heiman et al., 2008. Data was analyzed using Genespring GX10 software, as described in the text and in Doyle et al., 2008; Heiman et al., 2008. Briefly, samples were normalized using GCRMA, filtered to remove probe sets with low intensity, and analyzed using ANOVA (p<0.05) with SNK post-hoc and Benjamini and Hochberg FDR multiple testing correction. Probe quality, Pearson’s correlation, hierarchical clustering, heatmaps, gene profile plots were generated using Genespring GX10 software. Pathway analysis was performed using Ingenuity as per manufacturer’s instructions.
2011-06-17 | GSE30016 | GEO
Project description:Scnn1b-Tg mice overexpress the beta subunit of the epithelial sodium channel (Scnn1b) in airway Club cells. The general phenotype of these mice is described in three published manuscripts (Mall et al. 2004, Nature Medicine, 10(5):487-93; Mall et al. 2008, Am J Respir Crit Care Med. 177(7):730-42; Livraghi-Butrico et al. 2012, Physiol. Genomics 44(8):470-84; and Livraghi-Butrico et al. 2012, Mucosal Immunology 5(4):397-408). Briefly, overexpression of the Scnn1b transgene in airway Club cells leads to hyperabsorption of sodium from the airway surface liquid, which causes airway surface liquid and mucus dehydration, resulting in reduced mucus clearance and airway mucus obstruction. The data provided here represents mRNA expression data from dissected whole trachea (distal and proximal ends were cut 3-4 cartilage rings below the larynx and just above the bifurcation, respectively) from male WT and Scnn1b-Tg littermates (C57Bl/6N Tac background) at 4 time points [postnatal days (PND) 0, 3, 10, and 42]. Histologically, PND 0 trachea are normal, a tracheal mucus plug/obstruction develops around PND 3 and typically recedes to the intrapulmonary airways after PND 10, and the trachea is again histologically normal by PND 42. The data from the WT mice provides a global look at mRNA post-natal developmental changes, while the data from the Scnn1b-Tg line provides mRNA data that allows differential gene expression due to airway mucus obstruction to be queried. The data presented for the trachea is part of a larger body of work evaluating gene expression in whole lung, trachea, and purified macrophages.
2014-09-11 | GSE47550 | GEO
Project description:miR-142-3p is highly expressed in peripheral blood mononuclear cells (PBMCs) and has been described as a hematopoietic-restricted lineage, suggesting immune functions (Chen, Li et al. 2004; Landgraf, Rusu et al. 2007; Merkerova, Belickova et al. 2008). In order to determine the roles of miR-142-3p in B lymphocytes, we over-expressed this miRNA in the Raji B-cell line using a synthetic mimic of miR-142-3p and analyzed gene expression 24 hours after the transfection.
2011-05-30 | GSE28456 | GEO
Project description:Scnn1b-Tg mice overexpress the beta subunit of the epithelial sodium channel (Scnn1b) in airway Club cells. The general phenotype of these mice is described in three published manuscripts (Mall et al. 2004, Nature Medicine, 10(5):487-93; Mall et al. 2008, Am J Respir Crit Care Med. 177(7):730-42; and Livraghi-Butrico et al. 2012, Physiol. Genomics 44(8):470-84. Briefly, overexpression of the Scnn1b transgene in airway Club cells leads to hyperabsorption of sodium from the airway surface liquid, dehydrated airway surface liquid and mucus, and reduced mucus clearance associated with accumulation of mucus plugs/plaques. The data provided here represents mRNA expression data from disseccted whole trachea (distal and proximal ends cut 3-4 cartliage rings below the larynx and just above the bifurcation, respectively) from male WT and Scnn1b-Tg littermates (C57Bl/6NTac background) at 4 time points [postnatal days (PND) 0, 3, 10, and 42]. PND 0 trachea are histologically normal, a tracheal mucus plug/obstruction develops around PND 3, the plug is receding to more distal airways by PND 10, and the trachea is again histologically normal by PND 42. The data from the WT mice provides a global look at mRNA changes across time, while the data from the Scnn1b-Tg line provides mRNA data that allows differential gene expression due to mucus obstruction to be queried. The data presented for the purified is part of a larger body of work evaluating gene expression in whole lung, trachea, and purified macrophages.
2014-09-11 | GSE47548 | GEO
Project description:A robust set of CNS transcript changes was defined by comparing microarray data that describe the injury response of the rat retina [Vazquez-Chona et al., IOVS 2004; GSE1001], brain [Matzilevich et al., J Neurosci Res 2002; GSE1911], and spinal cord [Di Giovanni et al., Ann Neurol 2003; GDS63]. We determined the CNS injury genes that were expressed in cultured astrocytes from rat cortex [GSM34300] and from human optic nerve head [Yang et al., Physiol Genomics 2004; GDS532]. Keywords: other
2005-07-01 | GSE1928 | GEO
Project description:Interactions between cancer and immune cells determine the formation and progression of a tumor. Variability of immune contextures in tumor and margins among patients with oral squamous cell carcinoma of the gingivobuccal region (OSCC-GB) – the most prevalent subtype of oral cancer in India and southeast Asia – and the relationship of these contextures with prognosis are largely unknown. Treatment naïve, HPV negative, OSCC-GB patients (n=46) were recruited, treated, followed-up for two years and recurrence/death noted. Immune contextures of tumor and negative margins were studied using RNA-sequencing and immunohistochemistry (n=43; margin tissues were unavailable from three patients). Expressions of 544 immune related genes (IRGs) revealed a subgroup of patients (28%) with poor prognosis (high recurrence and death). The compositions of immune cell-types of normal and negative margin tissues were similar among patients irrespective of prognoses; differences were observed only in tumor.
2023-09-20 | GSE213862 | GEO
Project description:Homeobox genes are a family of transcription factors that play a pivotal role in embryogenesis. Altered expression of Prospero-related homeobox gene 1 (PROX1) was recently associated with cancer, including oral squamous cell carcinoma (OSCC). This study aimed to investigate the functional role of PROX1 in oral carcinogenesis. PROX1 mRNA and protein expression levels were first investigated in 40 samples of OSCC and non-tumour margins. Methylation and amplification analysis was also performed to assess the epigenetic mechanisms involved in controlling PROX1 expression. OSCC cell line SCC9 was also transfected to stably express the PROX1 gene. Next, SCC9-PROX1-overexpressing cells and controls were then subjected to proliferation, differentiation, apoptosis, and microarray assays in vitro. OSCC samples had reduced PROX1 expression levels compared to non-tumour margins. PROX1 amplification was associated with better overall survival. PROX1 overexpression reduces cell proliferation by down-regulating cyclin D1 and up-regulating p21. PROX1-overexpressing cells also exhibited significantly reduced K18 and K19 expression.
2014-12-30 | GSE48265 | GEO
Project description:A gene signature in histologically normal surgical margins is predictive of oral carcinoma recurrence
| PRJNA144853 | ENA
Project description:Comparison of polysomal profiles of murine adult olig2 cortical progenitors, murine tumor olig2 cells derived from hPDGF-B-driven glioblastomas, and murine olig2 proliferative recruited glioma cells contributing to the tumor mass but not derived from the cell of origin An unbiased way to define a cell population lies in identification of its gene expression signature and subsequent comparison to gene expression signatures of known normal or cancer cells to define its position on the axis of tumorigenesis. To quantify similarities and differences in the expression profiles of recruited cells and tumor cells using microarray analysis, we used the bacTRAP technology that allows immunoprecipitation of polysomes from specific cell types in vivo (Heiman et al 2008, Doyle et al 2008). We compared polysomal expression profiles of hPDGFb-driven Ntv-a Ink4a/Arf+/- olig2 mouse glioma cells representing a histologically defined glioma population, recruited olig2 cells derived from Ink4a/Arf+/- olig2 RP-eGFP mice transplanted with non-fluorescent glioma cells, and normal adult cortical olig2 mouse progenitors, using Affymetrix 430 mouse 2.0 chips and Genespring GX10 software (Doyle et al 2008, Heiman et al 2008). Translational profiles of recruited olig2 cells and glioma olig2 cells were similar to each other and clearly distinct from the normal olig2 progenitors, majority of the differences accounted for by the “statistically significantly changed” set of mRNAs (ANOVA, p<0.05), and sample clustering reduced upon removal of the ANOVA-tested mRNA set. Unsupervised hierarchical mRNA clustering likewise indicated that recruited olig2 cells clustered more closely to glioma olig2 cells. The caveat is that olig2 expression in the adult normal brain of bacTRAP olig2 RP-eGFP mice labels both progenitors and mature oligodendrocytes, while recruited and tumor olig2 cells are almost entirely progenitors; therefore, some of the differences seen in the comparative analysis of normal, tumor and recruited olig2 cells may in part result from the shift in relative abundance of different progenitor and mature olig2 cell populations. Normal olig2 progenitors were collected from three replicates of pooled cortices of three olig2 RP-eGFP bacTRAP reporter mice. Mouse gliomas induced by injection of a non-fluorescent RCAS-hPDGFb (Shih et al 2004) or by transplantation of muring glioma cells derived from Ntv-a gliomas induced by the non-fluorescent RCAS-hPDGFb were collected from Ntv-a olig2 RP-eGFP bacTRAP reporter mice and immunoprecipitated; each tumor was processed as a separate sample. Briefly, mouse tissues were collected into ice-cold cyclohexamide-containing buffer, homogenized, cells were lysed in NP-40 and DHPC-containing buffer, centrifuged at 20,000g for 15 min, supernatant incubated with anti-eGFP-conjugated protein G beads 30 min at 4C, washed and RNA collected using Trizol reagent as per manufacturer’s instructions (Doyle et al., 2008; Heiman et al., 2008). RNA was purified, concentrated using Qiagen RNeasy kit, its quality confirmed by Agilent Bioanalyzer, 15ng per sample amplified using Affymetrix Two-Cycle Amplification kit and hybridized to Affymetrix 430 mouse 2.0 chips as described in Doyle et al., 2008; Heiman et al., 2008. Data was analyzed using Genespring GX10 software, as described in the text and in Doyle et al., 2008; Heiman et al., 2008. Briefly, samples were normalized using GCRMA, filtered to remove probe sets with low intensity, and analyzed using ANOVA (p<0.05) with SNK post-hoc and Benjamini and Hochberg FDR multiple testing correction. Probe quality, Pearson’s correlation, hierarchical clustering, heatmaps, gene profile plots were generated using Genespring GX10 software. Pathway analysis was performed using Ingenuity as per manufacturer’s instructions. Gliomas are thought to form by clonal expansion from a single cell-of-origin, and progression-associated mutations to occur in its progeny cells. Glioma progression is associated with elevated growth factor signaling and loss of function of tumor suppressors Ink4a, Arf and Pten. Yet, gliomas are cellularly heterogeneous; they recruit and trap normal cells during infiltration. We performed lineage tracing in a retrovirally mediated, molecularly and histologically accurate mouse model of hPDGFb-driven gliomagenesis. We were able to distinguish cells in the tumor that were derived from the cell-of-origin from those that were not. Phenotypic, tumorogenic and expression analyses were performed on both populations of these cells. Here we show that during progression of hPDGFb-induced murine gliomas, tumor suppressor loss can expand the recruited cell population not derived from the cell-of-origin within glioma microenvironment to dominate regions of the tumor, with essentially no contribution from the progeny of glioma cell-of-origin. Moreover, the recruited cells can give rise to gliomas upon transplantation and passaging, acquire polysomal expression profiles and genetic aberrations typically present in glioma cells rather than normal progenitors, aid progeny cells in glioma initiation upon transplantation, and become independent of PDGFR signaling. These results indicate that non-cell-of-origin derived cells within glioma environment in the mouse can be corrupted to become bona fide tumor, and deviate from the generally established view of gliomagenesis.
2011-06-17 | E-GEOD-30016 | biostudies-arrayexpress